We have reported that extracorporeal immunosorption to remove circulating immune complexes (CIC) and IgG results in complete regression of feline lymphosarcoma infection (LSA) and a reversal of feline leukemia virus (FeLV). This was the first report of the therapeutic elimination of an oncoviral infection and also the first time that ex vivo immunosorption has been used to successfully treat LSA. We are proposing to investigate the possible mechanisms by which antiviral and antitumor responses may occur after ex vivo immunosorption therapy. We also propose to treat nonviral, feline mammary tumors (FeMT) by ex vivo immunosorption. In order to remove CIC that contain IgG for study, S. aureus Cowan I or protein A bound to a solid matrix will be used. Protein A, which is on the surface of S. aureus, binds nonspecifically to the Fc portion of IgG. Thus, it will be used as the immunosorbent. The immunosorbent will be mixed with the plasma of the treated (FeLV-LsA or FeMT) cats to remove CIC and the treated plasma returned to the host. The CIC can then be eluted from the immunosorbent for characterization. To better understand the mechanism of the anti-FeLV and antitumor response, the humoral and cell-mediated immunity of treated cats will be studied. The serum levels of FeLV antigens, FeLV-antibody and FOCMA antibody will be monitored during the course of treatments. Complement and CIC levels will be measured regularly to detect changes in these complements. We will study the biochemical nature of the molecules removed from the plasma of treated animals and quantitate the amounts of FeLV antigen and antibody to FOCMA antibody that may be in the circulating immune complexes removed by ex vivo immunosorption. The results of these studies will lead to a better understanding of the mechanism by which ex vivo immunosorption eliminates FeLV and induces LSA regression. Our studies may result in the development of better clinical treatments for cancer and also may provide basic information about the immunological interactions between the host and its tumor.